76 Participants Needed

Pembrolizumab + AR Inhibitors for Prostate Cancer

Recruiting at 3 trial locations
GR
Overseen ByGUONC Research Team
Age: 18+
Sex: Male
Trial Phase: Phase 1 & 2
Sponsor: Weill Medical College of Cornell University
Must be taking: LHRH/GnRH analogue
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This is a phase I/II study investigating the combination of 225Ac-J591 (a drug that can deliver radiation to prostate cancer cells) with pembrolizumab (immunotherapy, a drug that increases the immune system's ability to destroy cancer cells). This study will assess whether 225Ac-J591 + pembrolizumab + androgen receptor pathway inhibitor (ARPI) is more effective against prostate cancer than pembrolizumab + ARPI alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must continue primary androgen deprivation therapy if you haven't had an orchiectomy, and you can stay on bisphosphonates or denosumab if you've been on a stable dose for at least 4 weeks before starting the trial.

What data supports the effectiveness of the treatment Pembrolizumab + AR Inhibitors for Prostate Cancer?

Research shows that PSMA-targeted therapies, like 225Ac-J591, have been effective in treating prostate cancer by targeting a specific protein highly expressed in these cancer cells. Additionally, androgen receptor inhibitors, such as darolutamide, have shown success in treating prostate cancer by blocking hormones that fuel cancer growth.12345

Is the combination of Pembrolizumab and AR inhibitors safe for prostate cancer treatment?

The safety of 225Ac-J591, a component of the treatment, was evaluated in a study for prostate cancer, showing it was generally well-tolerated with a defined maximum tolerated dose. Another study on 225Ac-L1, a similar compound, showed some off-target effects mainly in the kidneys and liver, but it was considered promising for further evaluation. These findings suggest that while there are some risks, the treatment has been generally safe in studies.12678

How is the treatment with Pembrolizumab and AR Inhibitors for prostate cancer different from other treatments?

This treatment is unique because it combines Pembrolizumab, an immune therapy, with androgen receptor inhibitors and a targeted alpha therapy using 225Ac-J591, which delivers radiation directly to prostate cancer cells. This approach targets prostate-specific membrane antigen (PSMA) on cancer cells, potentially offering a more effective treatment for patients who have developed resistance to standard therapies.124910

Research Team

ST

Scott Tagawa, MD, MS

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has progressed after certain treatments. They must have a good performance status, normal organ function, and agree to contraception during the trial plus 4 months after. Exclusions include other cancers within 2 years, active infections like HIV or hepatitis, recent blood clots or radiotherapy, autoimmune diseases requiring treatment in the last 2 years, current participation in another study drug trial.

Inclusion Criteria

My testosterone levels are below 50 ng/dL, and I am on hormone therapy or have had an orchiectomy.
My blood counts and kidney, liver, and clotting functions are within normal ranges.
My prostate cancer is worsening, shown by rising PSA levels, new bone lesions, or growth in scans.
See 6 more

Exclusion Criteria

I have been on a stable dose of bisphosphonates or denosumab for over 4 weeks.
I haven't needed systemic treatment for an autoimmune disease in the last 2 years.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
See 22 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment Phase I

Participants receive pembrolizumab, ARPI, and a single dose of 225Ac-J591 to determine the optimal dose

12 weeks
Pembrolizumab every 6 weeks, 1 dose of 225Ac-J591

Safety Follow-up

Safety follow-up to monitor dose-limiting toxicity and determine optimal dose for phase II

12 weeks

Treatment Phase II

Randomized treatment with pembrolizumab and ARPI, with or without 225Ac-J591

Up to 2 years
Pembrolizumab every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 100 months
Imaging every 12 weeks

Treatment Details

Interventions

  • 225Ac-J591
  • Androgen receptor pathway inhibitor
  • Pembrolizumab
Trial OverviewThe trial is testing if adding a radioactive drug called 225Ac-J591 to pembrolizumab (an immunotherapy) and an ARPI (androgen receptor pathway inhibitor) can better fight prostate cancer than just pembrolizumab + ARPI. It's a phase I/II study which means they're looking at safety and effectiveness.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Pembrolizumab + ARPIExperimental Treatment3 Interventions
Patients will receive pembrolizumab (400mg every 6 weeks) and ARPI (standard dose schedule) without 225Ac-J591.
Group II: Pembrolizumab + 225Ac-J591 + ARPIExperimental Treatment4 Interventions
Patients will receive one dose of 225Ac-J591 (single dose, either 65 or 90 Kbq/kg) in combination with pembrolizumab (400mg every 6 weeks) and ARPI (standard dose schedule, examples of ARPI include enzalutamide and apalutamide).

Find a Clinic Near You

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials
1,103
Recruited
1,157,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials
4,096
Recruited
5,232,000+
Chirfi Guindo profile image

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis profile image

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

United States Department of Defense

Collaborator

Trials
940
Recruited
339,000+

Findings from Research

The combination of the androgen receptor inhibitor darolutamide and the PSMA-targeted thorium-227 conjugate (PSMA-TTC) showed synergistic antitumor efficacy in various prostate cancer models, including those resistant to other treatments.
Darolutamide increased the expression of PSMA, leading to enhanced uptake of PSMA-TTC in tumors and greater DNA damage, suggesting a promising new approach for treating prostate cancer that warrants further clinical investigation.
Darolutamide Potentiates the Antitumor Efficacy of a PSMA-targeted Thorium-227 Conjugate by a Dual Mode of Action in Prostate Cancer Models.Hammer, S., Schlicker, A., Zitzmann-Kolbe, S., et al.[2023]
The study of 32 patients with metastatic castration-resistant prostate cancer (mCRPC) showed that the radiolabeled antibody 225Ac-J591 is safe, with a maximum tolerated dose not reached and only one patient experiencing dose-limiting toxicity.
Preliminary efficacy results indicated that 46.9% of patients had at least a 50% decline in prostate-specific antigen (PSA) levels, and 59.1% showed a response in circulating tumor cell counts, suggesting potential effectiveness of this novel therapy.
Prostate-Specific Membrane Antigen-Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of 225Ac-J591.Tagawa, ST., Thomas, C., Sartor, AO., et al.[2023]
In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of [177Lu]Lu-PSMA-617 to standard care significantly delayed the time to first symptomatic skeletal event, with a median of 11.5 months compared to 6.8 months for standard care alone.
Patients receiving [177Lu]Lu-PSMA-617 also reported improved health-related quality of life and less pain, although there were some serious adverse events, including hematological issues, indicating the need for careful monitoring during treatment.
Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial.Fizazi, K., Herrmann, K., Krause, BJ., et al.[2023]

References

Darolutamide Potentiates the Antitumor Efficacy of a PSMA-targeted Thorium-227 Conjugate by a Dual Mode of Action in Prostate Cancer Models. [2023]
Prostate-Specific Membrane Antigen-Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of 225Ac-J591. [2023]
Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. [2023]
4.United Arab Emiratespubmed.ncbi.nlm.nih.gov
An Overview of Targeted Alpha Therapy with 225Actinium and 213Bismuth. [2019]
Radionuclide Treatment Yields Responses in mCRPC. [2020]
Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis. [2022]
Preclinical Evaluation of 213Bi- and 225Ac-Labeled Low-Molecular-Weight Compounds for Radiopharmaceutical Therapy of Prostate Cancer. [2022]
Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial. [2022]
68Ga-PSMA-11 PET Imaging of Response to Androgen Receptor Inhibition: First Human Experience. [2021]
Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic castration-resistant prostate cancer: a real-world study. [2023]